Search

Ten new sesquiterpenes, nardosinanols A-I ( 1- 9) and lemnafricanol ( 10), have been isolated from several Kenyan soft corals, i.e., from Lemnalia sp., Paralemnalia clavata, Lemnalia africana, and Rhytisma fulvum fulvum. The structures and relative stereochemistry of these compounds were elucidated by interpretation of MS, COSY ( (1)H- (1)H correlations), HSQC, HMBC, and NOESY NMR spectroscopic experiments and in the case of 5 also by chemical transformation to compounds 11 and 12. Nine compounds ( 1- 9) are based on the nardosinane skeleton ( 1- 6 are nardosinanes and 7- 9 nornardosinanes). Lemnafricanol ( 10) possesses a novel tricyclic skeleton. Compounds 3, 7, and 10 were found to be toxic to brine shrimp with LC 50 values of 4.0, 0.35, and 0.32 microM, respectively.

Two new polycyclic alkaloids, njaoamines G (1) and H (2) and 1,2,3,4-tetrahydroquinolin-4-one (3) have been isolated from the sponge Neopetrosia sp. collected at Pemba Island, Tanzania. Compounds 1 and 2 are close in structure to njaoamines A–F. Compound 3, known synthetically, is a new natural compound. The structures and relative stereochemistries of compounds 1 and 2 were elucidated on the basis of spectroscopic data. Njaoamines G and H are potent brine shrimp toxins with LD50 values of 0.17 μg/mL and 0.08 μg/mL for 1 and 2, respectively.

A large variety of unique heterocyclic natural marine products, without terrestrial counterparts, have been isolated from marine invertebrates, mainly sponges, ascidians, and soft corals. Many of these compounds display interesting biological activity. In this review, we report our recent studies on nitrogen-containing heterocyclic compounds ("alkaloids"), as well as some containing sulfur and oxygen, which have been isolated from Red Sea and Indo-Pacific organisms, and discuss progress on the synthesis of these natural products and structural analogs.

Seven new diterpenes, novaxenicins A–D (1–4) and xeniolides I–K (5–7), have been isolated from the Kenyan soft coral Xenia novaebrittanniae. The structures and relative stereochemistry of the compounds were elucidated by interpretation of MS, COSY, HSQC, HMBC, and NOESY experiments. The structure of novaxenicin A (1) was secured by X-ray diffraction analysis. Compound 5 possesses anti-bacterial activity at a concentration of 1.25 μg/ml and compound 2 induces apoptosis in transformed mammalian cells at a concentration of 1.25 μg/ml.

[structure: see text] Two novel ansa farnesyl quinols, designated likonides A and B, were isolated together with avarone from the Kenyan sponge Hyatella sp. The compounds are of a unique ansa structure. The structures and stereochemistry of the compounds were elucidated by interpretation of MS, two-dimensional NMR, and CD experiments.

A new alkaloid designated violatinctamine and four known metabolites were isolated from the tunicate Cystodytes cf. violatinctus collected in Kenya. Violatinctamine has a unique heterocyclic skeleton, which combines a benzothiazole unit and a dihydroisoquinoline unit. The structure of violatinctamine was elucidated by interpretation of MS results as well as 1D and 2D NMR spectra of the alkaloid and of its O , O ′-dimethyl derivative. Analysis of the spectral information also implies that violatinctamine exists as a mixture of two tautomers—the imino-phenol and the amino quinone-methide.

The isoprenoids comprise an important group among the marine natural products which are mainly obtained from soft corals, sponges and algae. The cembranes, xenia metabolites from soft corals and rearranged spongans from sponges are examples of marine diterpenoids obtained directly from GeGePP or after remarkable changes. Biogenesis, suggested biosynthesis, based on the structure and mainly known terrestrial biosynthesis, is proposed for diterpenoids and higher isoprenoids. Examples include the sipholanes, sodwanones and other triterpenoids as well as antheliolide and the T. toxius phenylhexaprenoide metabolites of mixed biogenetic origin.

Polyacetylenetriol (PAT), a natural marine product from the Mediterranean sea sponge Petrosia sp., was found to be a novel general potent inhibitor of DNA polymerases. It inhibits equally well the RNA- and DNA-dependent DNA polymerase activities of retroviral reverse transcriptases (RTs) (i.e. of HIV, murine leukaemia virus and mouse mammary tumour virus) as well as cellular DNA polymerases (i.e. DNA polymerases α and β and Escherichia coli polymerase I). A study of the mode and mechanism of the polymerase inhibition by PAT has been conducted with HIV-1 RT. PAT was shown to be a reversible non-competitive inhibitor. PAT binds RT independently and at a site different from that of the primer-template and dNTP substrates with high affinity (Ki = 0.51μM and Ki = 0.53μM with dTTP and with dGTP as the variable substrates respectively). Blocking the polar hydroxy groups of PAT has only a marginal effect on the inhibitory capacity, thus hydrophobic interactions are likely to play a major role in inhibiting RT. Preincubation of RT with the primer-template substrate prior to the interaction with PAT reduces substantially the inhibition capacity, probably by preventing these contacts. PAT does not interfere with the first step of polymerization, the binding of RT to DNA, nor does the inhibitor interfere with the binding of dNTP to RT/DNA complex, as evident from the steady-state kinetic study, whereby Km remains unchanged. We assume, therefore, that PAT interferes with subsequent catalytic steps of DNA polymerization. The inhibitor may alter the optimal stereochemistry of the polymerase active site relative to the primer terminus, bound dNTP and the metal ions that are crucial for efficient catalysis or, alternatively, may interfere with the thumb sub-domain movement and, thus, with the translocation of the primer-template following nucleotide incorporation.

Several new pyrido[2,3,4-kl]acridines were synthesized by reacting naphthoquinone, juglone or cyclohexan-1,3-dione with β,β’-diaminoketones in a biomimetic reaction. The structure of all new compounds was elucidated by NMR and MS spectroscopy. Electrophilic substitution, mainly nitration, of the various compounds was undertaken and the substitution positions determined. A series of derivatives was prepared and their cytotoxicity towards P-388 mouse lymphoma cells analysed. The most cytotoxic derivatives were found to have IC50’s of 0.05 and 0.1 ug/ml.

International audience; The relative configuration of tulearin A I (R3 = H, R8 = CONH2, R9 = H) was detd. by X-ray diffraction anal. of a cyclic carbonate deriv. I (R3 = H, R8R9 = CO), and the abs. configuration (2R,3R,5S,8S,9S,15R,17S) from the 9-MTPA-esters I [R3 = H, R8 = CONH2, R9 = COC(OMe)(CF3)Ph-(R), -(S)] was detd. using the modified Mosher's method. A mechanism for the unexpected formation of the cyclic carbonate was suggested. Two N-phenyltriazolinedione cycloadducts of tulearin A were also prepd. Two addnl. tulearins, B and C I (R3 = CONH2, R8 = CONH2, R9 = H; R3 = H, R8 = H, R9 = H, resp.), were isolated in very small amts. from Fascaplysinopsis, and their structures are elucidated by spectroscopic means. [on SciFinder(R)]

By applying the cyclic endiamino cyclisation methodology to linear tripeptides embodying a β-turn-directing amino acid, the imidazopyrazine ring system was afforded. A mechanism involving the originally desired nine-membered cyclic endiamine is suggested. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Polycitone A, an aromatic alkaloid isolated from the ascidian Polycitorsp. exhibits potent inhibitory capacity of both RNA- and DNA-directed DNA polymerases. The drug inhibits retroviral reverse transcriptase (RT) [i.e. of human immunodeficiency virus type 1 (HIV), murine leukaemia virus (MLV) and mouse mammary tumour virus (MMTV)] as efficiently as cellular DNA polymerases (i.e. of both DNA polymerases α and β and Escherichia coliDNA polymerase I). The mode and mechanism of inhibition of the DNA-polymerase activity associated with HIV-1 RT by polycitone A have been studied. The results suggest that the inhibitory capacity of the DNA polymerase activity is independent of the template-primer used. The RNase H function, on the other hand, is hardly affected by this inhibitor. Polycitone A has been shown to interfere with DNA primer extension as well as with the formation of the RT-DNA complex. Steady-state kinetic studies demonstrate that this inhibitor can be considered as an allosteric inhibitor of HIV-1 RT. The target site on the enzyme may be also spatially related to the substrate binding site, since this inhibitor behaves competitively with respect to dTTP with poly(rA)˙oligo(dT) as template primer. Chemical transformations of the five phenol groups of polycitone A by methoxy groups have a determinant effect on the inhibitory potency. Thus, the pentamethoxy derivative which is devoid of all hydroxy moieties, loses significantly, by 40-fold, the ability to inhibit the DNA polymerase function. Furthermore, this analogue lacks the ability to inhibit DNA primer extension as well as the formation of the RT-DNA complex. Indeed, inhibition of the first step in DNA polymerization, the formation of the RT-DNA complex, and hence, of the overall process, could serve as a model for a universal inhibitor of the superfamily of DNA polymerases.

Ten new isoprenoids have been isolated from two marine sponges Ptilocaulis spiculifer and Axinella weltneri. P. spiculifer afforded three triterpenes, dihydroyardenone ( 1 ), abudinol B ( 2 ), muzitone ( 3 ) and two C 13 and C 17 metabolites of abudinol, nakorone ( 4 ) and durgamone ( 5 ). A. weltneri gave five new sodwanones, N-R ( 6 – 10 ). The structures of all new compounds were elucidated by spectroscopic analyses, mainly NMR data, and by chemical transformations to known compounds and degradations. The absolute configuration of several compounds was determined by optical measurements and comparison of the CD-curves with those of several raspacionins. Several sodwanones were found to be cytotoxic.

Two novel cyclic hexapeptides, comoramides A and B and two new cyclic heptapeptides, mayotamides A and B were isolated, separately, from two collections of the compound ascidian Didemnum molle collected at two spots of the lagoon of Mayotte. The structure of all four peptides, including the absolute configuration of all amino acids, was elucidated by spectroscopic analysis, mainly NMR data, and degradation experiments. All four compounds exhibit mild cytotoxicity against several tumor cells. Obtaining four new cyclic peptides from two D. molle collections, which add to the two earlier reported cyclic peptides from an Australian and Philippine D. molle , supports the notion that these compounds originate from prokaryotic algal symbionts.

Three novel nitrogen-containing metabolites, asmarines A-C (1 – 3) together with two known diterpenes, zaatirin and chelodane were isolated from the Red Sea sponge Raspailia sp. collected in the Dahlak archipelago, Eritrea. The structure of the three new compounds and the known zaatirin and chelodane were established by spectroscopic analysis including X-ray diffraction analysis for asmarine A. Asmarines A-C are cytotoxic to a few human cancer cells.

Two novel triterpenes, yardenone ( 5 ) and abudinol ( 6 ) together with the known sodwanones A-D ( 1 – 4 ) have been isolated from the marine sponge Ptilocaulis spiculifer . The structures of compounds 5 and 6 were determined by interpretation of their 1D and 2D NMR spectra and were secured, including their relative stereochemistry, by X-ray diffraction analysis.

A new norcembrane, designated sinularectin 3 , was isolated from the Kenyan soft coral Sinularia erecta. Sinularectin is a chlorinated highly oxygenated norcembrane with an unprecedented functionalisation of the cembrane isopropyl group. The structure of sinularectin was elucidated by interpretation of the HRESMS results as well as 1D and 2D NMR spectra.

Three new triterpenes, sodwanones M, K, and L (4, 5, 6), together with three known sodwanones (A, B, and D) have been isolated from the sponge Axinella weltneri from the Comoros Islands, in the Indian Ocean. The three new structures were determined by interpretation of NMR spectra and, in the case of sodwanone K, also by oxidation to the known sodwanone D. Sodwanone M, the major isolated compound, was found to be cytotoxic to P-388 murine leukemia cells at a concentration of 1 microgram/mL.

Interleukin-11 (IL-11) is a novel cytokine that has been shown to stimulate human hematopoietic progenitors including the CD34+ CD33- DR- early progenitors. IL-11 has little effect on its own but it synergizes with other hematopoietic growth factors. We investigated the recovery of human myeloid progenitors incubated with IL-11 alone or in combination with other cytokines, including stem cell factor (SCF), interleukin-3 (IL-3) and granulocyte macrophage colony-stimulating factor (GM-CSF) following their in vitro treatment with ARA-C (10(-9) M) or Eilatin (10(-7) M). IL-11 in combination with IL-3 and GM-CSF markedly increased CFU-C colony growth pre- and post-ARA-C or Eilatin incubation from CML and normal individual bone marrow (BM) cells. Similarly, IL-11 alone or in combination with other cytokines increased cell recovery following 7-day suspension culture. A decrease in BCR/ABL fusion product was observed (by FISH analysis) after incubation of BM cells from CML patients in liquid culture for 7 days with 10(-9) M ARA-C or 10(-7) M Eilatin in the presence of IL-11 alone or in combination with other cytokines. These results indicate that following cytoreductive therapy IL-11 may enhance to a greater extent the growth of normal myeloid progenitors than the malignant clone and may, therefore, be of clinical importance for CML patients treated with chemotherapeutic agents.

Four new tetraprenyltoluquinols (2−5) have been isolated from the Indo-Pacific soft corals Sinularia dura and Nephthea sp. Sindurol (2), isolated from the Sinularia, is a 1,3,5-trialkylated 2,8-dioxabicyclo[3.2.1]octane, and nephthoside (4), obtained from the Nephthea, is a new substituted hydroquinone d-arabinose glycoside. Compounds 3 and 5 are closely related to nephthoside (4). The structure determination of all new compounds was based mainly on 1D- and 2D-NMR spectroscopy and mass spectrometry, as well as some chemical transformations.

Antheliatin [1], zahavin A [2], and zahavin B [3], three novel xenicane diterpenoids, have been isolated from two Indo-Pacific soft corals, Anthelia glauca and Alcyonium aureum. The two species belong to different families of reef-inhabiting soft corals. The structures of compounds 1-3 were established on the basis of X-ray and 1D and 2D nmr data.

Two novel cyclic hexapeptides, didmolamides A and B, were isolated from the compound ascidian Didemnum molle collected in Madagascar. The structure of the two peptides was elucidated by interpretation of MS, COSY, HMQC, and HMBC data. The absolute configuration of all amino acids was determined to be l using Marfey's method for HPLC.

The organic extract of Xenia faraunensis was found to contain besides xeniolide A and B three novel diterpenes: xeniafaraunol A (1), -B (2) and faraunatin (3). The structure of compounds 1–3 was defined by spectral methods and mainly 1D and 2D NMR experiments. Xeniafaraunol A and B (1 and 2) are of a novel bicyclo[7.4.0] tridecane carbon skeleton and faraunatin (3) is an unprecedented prenylated bicyclogermacrene. Compounds 1–3 are cytotoxic against P388 cells.

Three new sesquiterpene hydroquinones peyssonol A and B (5 and 6 and hyatellaquinone (7) have been isolated from the alga Peyssonnelia sp. and the sponge Hyatella intestinalis. The structure of the three compounds was determined mainly by NMR measurements. Peyssonol A (5) is the first reported bromo sesquiterpene hydroquinone. Several of the new compounds were found in a preliminary test to inhibit the reverse transcriptase of human immunodeficiency virus (HIV).

Four new chlorinated phenylpyrrolyloxazoles, phorbazoles AD (1a-4) have been isolated from the sponge Phorbas aff clathrata. The structure of phorbazole A was unambiguously determined by X-ray diffraction studies of its dimethyl derivative (1b). The structures of compounds 2–4 were determined by extensive use of 1D and 2D NMR techniques. Phorbazoles AD represent a new class of marine alkaloids embodying the previously unprecedented, chlorinated pyrrole moiety, from marine sources.

The natural product of the Red Sea sponge Verongia sp., identified as 3,5,8-trihydroxy-4-quinolone, was found to be a potent inhibitor of the RNA-directed DNA synthesis of the reverse transcriptases (RTs) of human immunodeficiency viruses type 1 and type 2 (HIV-1 and HIV-2, respectively). This inhibition was unaffected by the nature of the primer template used for DNA synthesis. The DNA-dependent DNA polymerase activity was inhibited to a lesser extent, whereas the ribonuclease H (RNase H) function associated with both HIV RTs was only slightly inhibited. The inhibition by the trihydroxyquinolone is reversible and noncompetitive with respect to both substrates-dTTP and the template primer poly(rA) n · oligo(dT) 12-18 . The inhibitor binds HIV-1 RT with a high affinity ( K i = 0.46 μM). This compound was shown also to inhibit the catalytic activities of the RT of murine leukemia virus, establishing the general inhibitory effect on retroviral RTs. Introductions of acetyl or methoxy moieties at positions with potential activity have generated three synthetic analogs of the natural compound. Only one analog, 5,8-dimethoxy-4-quinolone, exhibited an inhibition potency similar to that of the unmodified compound. Analysis of the three analogs has led us to the conclusion that the hydroxyl group at the ortho position to the carbonyl group in the pyridinone ring is a key structural element for the inhibitory activity. Thus, it could well be that the inhibitor interacts with the enzyme through a hydrogen bond of this hydroxyl group. We hope that the identification of the inhibitory site of the compound might be an important step toward the rational design of new potent anti-HTV RT drugs.

A biomimetic reaction between β,β′-diamenoketones (e.g. kynuramine, kynurenine or o,o′-diaminobenzophenone) and a variety cyclohexanediones and quinones leading to pyrido[2,3,4-kl) acridines is described. The synthesis of several di- and tetrahydro-pyrido[2,3,4-kl)acridine derivatives (7, 10. 12 and 15) as well as benzoderivatives of the marine alkaloids eilatin (1) and ascididemin (2), compounds 28 and 30, has been accomplished. Additionally, the new heterocycles isoeilatin (24), and diazapentacene 19 have also been synthesized. All newly prepared heterocycles have been fully characterized by IR, MS and mainly by NMR spectroscopy. An analogous synthesis has been developed for pyrrolo[2,3,4-kl)acridines, the heterocyclic core of the bioactive marine alkaloids the plakinidines (31 A-C).

Lemnaflavoside (1) and three monoacetates (2-4) have been isolated from the Indo-Pacific soft coral Lemnalia flava, collected off Mombasa, Kenya. The structure of the new glycoside was elucidated by interpretation of MS and 2D NMR data. The sugar of the diterpene glycoside was found to be D-xylose.

A short new biomimetic route to the pyrido[2,3,4- kl ]acridine ring system has been developed from readily available benzoquinone, or hydroquinone precursors, and β,β′-diaminoketones like kynuramine ( 3 ) or 2,2′-diaminobenzophenone ( 4 ), involving one key step. Pyrido[2,3,4- kl ]acridine and closely related compounds have been prepared ( 5–9 ). The reaction has been shown to proceed to the formation of 1:1 and/or 1:2 quinone/amine adducts. Using of o-aminoacetophenone afforded dibenzo[1,10]phenanthrolinedione ( 11 ) a potential intermediate to eilatin 2 .

Asmarines are marine alkaloids with the unique N(10)-hydroxytetrahydro[1,4] diazepino[1,2,3-g,h]purine system and interesting biological activity. The heterotricyclic system was prepared from substituted purines. CH-correlations were found to be an easy way to determine the mode of cyclisation in those cases where more than one is possible, that is, obtaining the tetrahydrodiazepinopurine or tetrahydropyrimidopurine system.

Two new syntheses have been developed for the preparation of substituted pyrido[2,3,4-kl]acridines. The first synthesis involves a Skraup reaction and a nitrene insertion whereas the second includes a new pyridine ring synthesis starting from a 1-amino group on acridine and taking advantage of the active 9-position of the latter heterocycle.

A short new biomimetic route to the pyrido[2,3,4- kl ]acridine ring system has been developed from readily available benzoquinone, or hydroquinone precursors, and β,β′-diaminoketones like kynuramine ( 3 ) or 2,2′-diaminobenzophenone ( 4 ), involving one key step. Pyrido[2,3,4- kl ]acridine and closely related compounds have been prepared ( 5–9 ). The reaction has been shown to proceed to the formation of 1:1 and/or 1:2 quinone/amine adducts. Using of o-aminoacetophenone afforded dibenzo[1,10]phenanthrolinedione ( 11 ) a potential intermediate to eilatin 2 .

Three novel compound polycitone A (1a) and polycitrins A and B (2 and 3) were isolated from the marine ascidian Polycitor sp. The structures of compounds 1a, 2, and 3 were established mainly on the basis of NMR spectroscopic data and, in the case of 1a, also by single-crystal X-ray diffraction analysis. The crystallographic analysis was performed on 1b, the penta-O-methyl derivative of 1a, both compound yielding poorly diffracting crystals of highly anisotropic shape. It required, in view of the dominating heavy-atom content of 1b, diffraction measurements with an intense rotating-anode X-ray source. Polycitone A and polycitrins A and B represent the first examples of two new classes of marine products which might biogenetically be close to the lamellarins. The penta-O-methyl derivatives 1b, was found to inhibit the growth of SV40 transformed fibroblast cells in a concentration of 10 μg/mL

A two-step biomimetic synthesis of the pentacyclic pyrido[2,3,4-kl]acridine marine alkaloid ascididemin (3a) from quinolinequinone 5a and N-trifluoroacetamidokynuramine (4) is described. The crucial step (6 to 7) involves the simultaneous formation of two pyridine rings in a process which might well offer an explanation for the biogenetic synthesis in marine organisms. The preparation of substituted ascididemins by either starting from substituted quinoline-quinones, e.g., 5b to afford 11-methoxyascididemin (3b), or by nitration of 3a to the mono 1- or 3-nitroascididemins (8 and 9 respectively) is reported

Three cytotoxic triterpenes, sodwanones G [5], H [6], and I [7], have been isolated from a marine sponge. The three structures were determined by interpretation of nmr spectra, and in the case of 5, also on the basis of the X-ray diffraction analysis. The X-ray diffraction analysis of two other earlier reported sodwanones, E [3] and F [4] is also discussed. The cytotoxic activity against several cancer cell lines, has been tested. IC50 values between 20 and 0.02 microM were obtained. Compounds 5 and 6 were 10- and 500-fold, respectively, more cytotoxic to A-549 cells than to any of the other cell lines tested (HT-29, MEL-28, P-388).

Two novel triterpenes, yardenone ( 5 ) and abudinol ( 6 ) together with the known sodwanones A-D ( 1 – 4 ) have been isolated from the marine sponge Ptilocaulis spiculifer . The structures of compounds 5 and 6 were determined by interpretation of their 1D and 2D NMR spectra and were secured, including their relative stereochemistry, by X-ray diffraction analysis.

Three novel nitrogen-containing metabolites, asmarines A-C (1 – 3) together with two known diterpenes, zaatirin and chelodane were isolated from the Red Sea sponge Raspailia sp. collected in the Dahlak archipelago, Eritrea. The structure of the three new compounds and the known zaatirin and chelodane were established by spectroscopic analysis including X-ray diffraction analysis for asmarine A. Asmarines A-C are cytotoxic to a few human cancer cells.

Two novel cyclic hexapeptides, comoramides A and B and two new cyclic heptapeptides, mayotamides A and B were isolated, separately, from two collections of the compound ascidian Didemnum molle collected at two spots of the lagoon of Mayotte. The structure of all four peptides, including the absolute configuration of all amino acids, was elucidated by spectroscopic analysis, mainly NMR data, and degradation experiments. All four compounds exhibit mild cytotoxicity against several tumor cells. Obtaining four new cyclic peptides from two D. molle collections, which add to the two earlier reported cyclic peptides from an Australian and Philippine D. molle , supports the notion that these compounds originate from prokaryotic algal symbionts.

[formula: see text] Two novel sesterpenes, bilosespens A and B (1 and 2) were isolated from the Red Sea sponge Dysidea cinerea collected in the Dahlak archipelago, Eritrea. The structure of the mixture of the two inseparable compounds was established by spectroscopic analysis, mainly by 1D and 2D NMR measurements. The mixture of bilosespens A and B is cytotoxic to a few human cancer cells.

Two novel alpha-oxoamides, salaramide A (1) and its homologue salaramide B (2), were isolated from the Madagascar marine sponge, Hippospongia sp., collected in Salary Bay, north of Tulear. The structures of 1 and 2 were elucidated by interpretation of mass spectra, 1D and 2D NMR spectra, and confirmed by chemical transformation.

Seven new nitrogenous macrolides, designated salarins D–J (4–10), closely related to salarins A–C (1–3), have been isolated from the Madagascar Fascaplysinopsis sp. sponge. The structure and relative stereochemistry of compounds 4–10 were elucidated by interpretation of MS, COSY, HSQC, HMBC, and NOESY spectra. Salarin B's structure (2), based on the structure of salarin J (10), is now amended to also incorporate the C-14 to -17 THF ring system. All compounds were evaluated for their cytotoxicity against K562 and UT-7 human leukemia cells. While salarins D, E, H, and J displayed dose and time dependent inhibition of proliferation, salarins F and I were not active in these assays.

International audience; A new steroidal alkaloid, plakinamine L (1) with an unprecedented acyclic side chain, was isolated from the marine sponge Corticium sp. collected near Salary (south-west of Madagascar). The structure was elucidated by combined spectroscopic methods.

International audience; Two novel α-oxoamides, salaramide A (1) and its homolog salaramide B (2), were isolated from the Madagascar marine sponge, Hippospongia sp., collected in Salary Bay, north of Tulear. The structures of 1 and 2 were elucidated by interpretation of mass spectra, 1D and 2D NMR spectra, and confirmed by chem. transformation. [on SciFinder(R)]

Three new diterpenoids, chelodane {1}, barekoxide {2}, and zaatirin {3}, were isolated from a marine sponge, Chelonaplysilla erecta, collected in the Red Sea. The structure determination of the three compounds, which belong to three different types of diterpenoids, was achieved by 1D and mainly 2D nmr measurements

Two new syntheses have been developed for the preparation of substituted pyrido[2,3,4-kl]acridines. The first synthesis involves a Skraup reaction and a nitrene insertion whereas the second includes a new pyridine ring synthesis starting from a 1-amino group on acridine and taking advantage of the active 9-position of the latter heterocycle.